University of Denver, Department of Biological Sciences, Denver, CO 80210, USA.
Gen Comp Endocrinol. 2013 Jan 15;181:203-10. doi: 10.1016/j.ygcen.2012.11.011. Epub 2012 Nov 29.
When considering the interactions between the melanocortin peptides (i.e., ACTH, α-MSH, β-MSH, γ-MSH) and the melanocortin receptors (i.e., MC1R, MC2R, MC3R, MC4R, MC5R), it appears that the structure/function relationship between ACTH and MC2R is the most complicated. Human ACTH(1-24) and the human melanocortin-2 receptor provide a useful model system for understanding how ACTH emerged as the sole ligand for the melanocortin-2 receptor of bony vertebrates. This review will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for activation of the melanocortin-2 receptor. In addition, observations on the unique activation features of the melanocortin-2 receptor, as revealed from studies on Familial Glucocorticoid Deficiency, will be considered. Finally, the evolutionary implications of the relationship between MC2R and MRAP1 will be discussed.
当考虑黑素细胞刺激素肽（即 ACTH、α-MSH、β-MSH、γ-MSH）与黑素细胞刺激素受体（即 MC1R、MC2R、MC3R、MC4R、MC5R）之间的相互作用时，ACTH 与 MC2R 之间的结构/功能关系似乎最为复杂。人类 ACTH(1-24) 和人类黑素细胞刺激素-2 受体为理解 ACTH 如何成为骨脊椎动物黑素细胞刺激素-2 受体的唯一配体提供了一个有用的模型系统。本综述将讨论利用 hACTH(1-24) 类似物的研究如何揭示该配体中两个关键的氨基酸基序（HFRW 和 KKRRP），这些基序对于激活黑素细胞刺激素-2 受体是必需的。此外，还将考虑从家族性糖皮质激素缺乏症研究中揭示的黑素细胞刺激素-2 受体的独特激活特征的观察结果。最后，将讨论 MC2R 和 MRAP1 之间关系的进化意义。
